Chemistry Reference
In-Depth Information
O
H
COCl
2
O
l
H
3
C
H
3
C
+
CO
2
O
Cl
1363
1364
H
O
CH
3
OCCl
2
COCl
COOH
H
3
C
+
+
HCl
O
92.5 %
1365
1366
1367
CH
3
O
CH
3
O
H
O
CH
3
OCCl
2
H
3
C
+
+
HCl
H
3
C
Cl
H
3
C
OH
O
O
O
98 %
1368
1369
1367
A report of the synthesis of acid anhydrides using phosgene gas has also ap-
peared in the literature [1040, 1041]. Nicotinic anhydride 1371 was prepared from
nicotinic acid 1370 with phosgene in 87-93% yield, as described in a very detailed
procedure [1041].
O
O
CO
2
H
COCl
2
O
TEA
benzene
N
N
N
87-93 %
1371
1370
Typical procedure. Nicotinic anhydride 1371 [1041]:
Nicotinic acid 1370 (10 g, 0.081
mol) and anhydrous benzene (275 mL) were placed in a 500-mL, three-necked,
round-bottomed flask (dried overnight in an oven at 200
C) fitted with a sealed
Hershberg stirrer, a dropping funnel with a pressure-equalizing tube, and a still-
head connected to a condenser. In order to remove traces of moisture introduced
with the nicotinic acid, the mixture was heated until about 75 mL of the benzene
had distilled. The stillhead was then replaced by a Claisen head fitted with a ther-
mometer and a calcium chloride guard tube, and the mixture was cooled to 5
Cby
stirring in an ice bath. To the cold suspension of nicotinic acid, freshly distilled
triethylamine (8.65 g, 0.086 mol, 5% excess) was added in a single portion. The
resulting clear solution was stirred with continued cooling while phosgene (for a
safe source and for safe phosgenation, see Chapter 7) (34 g of a 12.5% solution in
benzene, 0.043 mol, 5% excess) was added from the dropping funnel. The rate of
addition was regulated so that the temperature of the reaction mixture did not ex-
ceed 7
C. Triethylamine hydrochloride precipitated immediately. After the addi-
